- Synthesis of new phenolic compounds and biological evaluation as antiproliferative agents
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New series of phenolic azomethine compounds in addition to 5-arylidene thiazolidinones are synthesized and screened for their anticancer activity against the brain cancer cell line SNB-75 and non-small lung cancer cells HOP-92. The azomethine derivative 12b is the most active compound against SNB-75 displaying an IC50 value of 0.14 μM. Compounds 7b, 16a and 27d display submicromolar activity against the HOP-92 cell line with IC50 values of 0.73, 0.74 and 0.81 μM, respectively. Moreover, studying the cytotoxic effects of the most active compounds against normal lung cells WI-38 revealed that compounds 7b, 16a and 27d showed high safety profiles as anticancer agents.
- Ibrahim, Marwa A,George, Riham F,Abou-Seri, Sahar M,El-Moghazy, Samir M
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p. 181 - 192
(2020/01/06)
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- Affinity adsorption mechanism studies of adsorbents C1-Zn(II) for uremic middle molecular peptides containing Asp-Phe-Leu-Ala-Glu sequence
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To exploit efficient adsorbents for removing middle molecular peptides containing DFLAE (DE5, a typical peptide sequence accumulated in uremic serum) sequence by hemoperfusion, we designed and synthesized three affinity adsorbents (C1-Zn2+, C2-Zn2+ and C3-Zn2+) that could have high affinity to DE5. Subsequently, we evaluated the corresponding adsorption ability of each adsorbent by static adsorption experiments and isothermal titration calorimetry (ITC). The results showed that C1-Zn2+ had the best adsorption ability to DE5-containing peptides and the adsorption capacity for DE5 was 8.52 mg/g. By changing the adsorption conditions, the adsorption mechanism was elucidated. The main driving force of the adsorption is metal-carboxyl coordination and the hydrophobic force affords the cooperative effect. It is expected that our present work can provide basic understanding for the design of adsorbents with high affinity and selectivity towards oligopeptides.
- Li, Pinglin,Fu, Lixue,Qiao, Yitao,Zhao, Jianxin,Wang, Wei,Yuan, Zhi
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experimental part
p. 375 - 379
(2012/02/03)
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- Adsorbents with high selectivity for uremic middle molecular peptides containing the Asp-Phe-Leu-Ala-Glu sequence
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Asp-Phe-Leu-Ala-Glu (DE5) is a frequent sequence of many toxic middle molecular peptides that accumulate in uremic patients. To eliminate these peptides by hemoperfusion, three adsorbents (CP1-Zn2+, CP2-Zn 2+, and CP3-Zn2+) were designed on the basis of coordination and hydrophobic interactions. Adsorption experiments indicated that CP2-Zn2+ had the highest affinity for DE5 among these three adsorbents. Also, the adsorption capacity of CP2-Zn2+ in DE5 and DE5-containing peptides was about 2-6 times higher than that of peptides without the DE5 sequence. Linear polymers bearing the same functional groups of the adsorbents were used as models to study the adsorption mechanism via isothermal titration calorimetry (ITC) and computer-aided analyses. The results indicated that coordination and hydrophobic interactions played the most important roles in their affinity. When two carboxyl moieties on Asp and Glu residues coordinated to CP2-Zn2+, the hydrophobic interaction took place by the aggregation of the hydrophobic amino acid residues with phenyl group on CP2-Zn2+. The optimal collaboration of these interactions led to the tight binding and selective adsorption of DE5-containing peptides onto CP2-Zn2+. These results may provide new insight into the design of affinity adsorbents for peptides containing DE5-like sequences.
- Qiao, Yitao,Zhao, Jianxin,Li, Pinglin,Wang, Jun,Feng, Jing,Wang, Wei,Sun, Hongwei,Ma, Yi,Yuan, Zhi
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experimental part
p. 7181 - 7187
(2010/12/25)
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- Nonpeptide inhibitors of measles virus entry
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Measles virus (MV) is one of the most infectious pathogens known. Despite the existence of a vaccine, over 500 000 deaths/year result from MV or associated complications. Anti-measles compounds could conceivably reverse these statistics. Previously, we described a homology model of the MV fusion protein trimer and a putative binding site near the head-neck region. The resulting model permitted the identification of two nonpeptidic entry inhibitors. Here, we present the design, synthesis, and bioevaluation of several series of fusion inhibitors and describe their structure-activity relationships (SAR). Five simply substituted anilides show low-μM blockade of the MV, one of which (AS-48) exhibits IC50 = 0.6-3.0 μM across a panel of wild-type MV strains found in the field. Molecular field topology analysis (MFTA), a 2D QSAR approach based on local molecular properties (atomic charges, hydrogen-bonding capacity and local lipophilicity), applied to the anilide series suggests structural modifications to improve potency.
- Sun, Aiming,Prussia, Andrew,Zhan, Weiqiang,Murray, Ernest E.,Doyle, Joshua,Cheng, Li-Ting,Yoon, Jeong-Joong,Radchenko, Eugene V.,Palyulin, Vladimir A.,Compans, Richard W.,Liotta, Dennis C.,Plemper, Richard K.,Snyder, James P.
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p. 5080 - 5092
(2007/10/03)
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- NOVEL AMIDE COMPOUNDS
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A compound of the formula (I):R1-A-X-NHCO-Y-R2 ???whereinR1 is heterocyclic group which may have suitable substituents, or phenyl which may have suitable substituents,R2 is condensed phenyl which may have suitable substituents, phenyl which may have suitable substituents, or thienyl which may have suitable substituents,A is a group of the formula:-(CH2)t-(O)m- or in which R3 and R4 are each hydrogen or linked together to form imino,R5 is hydrogen or lower alkyl,t is 0, 1 or 2,p, m and n are each 0 or 1,X is phenylene which may have suitable substituents, or bivalent heterocyclic group containing nitrogen which may have suitable substituents,Y is bond, lower alkylene, or lower alkenylene, and a salt thereof.
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